title: Protective role of a coumarin-derived schiff base scaffold against tertiary butyl hydroperoxide (TBHP)-induced oxidative impairment and cell death via MAPKs, NF-κB and mitochondria-dependent pathways.
abstract: The present study investigated the antioxidant signalling mechanism of a coumarin-derived schiff base (CSB) scaffold against tert-butylhydroperoxide (TBHP) induced oxidative insult in murine hepatocytes. CSB possesses DPPH and other free radical scavenging activities. TBHP reduced cell viability and intracellular antioxidant status accompanied by an increase in intracellular ROS production in hepatocytes. TBHP also activated phospho-ERK1/2, phospho-p38 and NF-κB, altered the Bcl-2/Bad ratio, reduced mitochondrial membrane potential, released cytochrome C and activated caspase 3, suggesting that TBHP induced oxidative stress responsive cell death via apoptotic pathway. FACS analysis and DNA fragmentation studies also confirmed the apoptotic cell death in TBHP exposed hepatocytes. Treatment with CSB effectively reduced these adverse effects by preventing the oxidative insult, alteration in the redox-sensitive signalling cascades and mitochondrial events. Combining, results suggest that antioxidant property of CSB make the molecule to be a potential protective measure against oxidative insult, cytotoxicity and cell death.
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054, India.
authors.forename: Manoranjan
authors.initials: M
authors.lastname: Ghosh
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Manna
authors.forename: Parames C
authors.initials: PC
authors.lastname: Sil
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000819:agonists / Q000138:chemical synthesis / Q000494:pharmacology*; D019610:Cytoprotection; D053938:DNA Fragmentation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000494:pharmacology; D012545:Schiff Bases / Q000138:chemical synthesis / Q000494:pharmacology*; D020122:tert-Butylhydroperoxide / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D003374:Coumarins; D016166:Free Radical Scavengers; D005609:Free Radicals; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D012545:Schiff Bases; D020122:tert-Butylhydroperoxide; C030123:coumarin; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3